Suppression of tumor growth in H-ras12V liver cancer mice by delivery of programmed cell death protein 4 using galactosylated poly(ethylene glycol)-chitosan-graft-spermine

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Title
Suppression of tumor growth in H-ras12V liver cancer mice by delivery of programmed cell death protein 4 using galactosylated poly(ethylene glycol)-chitosan-graft-spermine
Author(s)
J H Kim; A Minai-Tehrani; Y K Kim; J Y Shin; S H Hong; H J Kim; H D Lee; S H Chang; K N Yu; Y B Bang; C S Cho; T J Yoon; Dae Yeul Yu; H L Jiang; M H Cho
Bibliographic Citation
Biomaterials, vol. 33, no. 6, pp. 1894-1902
Publication Year
2012
Abstract
Non-viral gene delivery systems based on polyethyleneimine (PEI) are efficient due to their proton-sponge effect within endosomes, but they have poor physical characteristics such as slow dissociation, cytotoxicity, and non targeted gene delivery. To overcome many of the problems associated with PEI, we synthesized a galactosylated poly(ethylene glycol)-chitosan-graft-spermine (GPCS) copolymer with low cytotoxicity and optimal gene delivery to hepatocytes using an amide bond between galactosylated poly(ethylene glycol) and chitosan-graft-spermine. The GPCS copolymer formed complexes with plasmid DNA, and the GPCS/DNA complexes had well-formed spherical shapes. The GPCS/DNA complexes were nanoscale size with homogenous size distribution and a positive zeta potential by dynamic light scattering (DLS). The GPCS copolymer had lower cytotoxicity than that of PEI 25K in HepG2, HeLa, and A549 cell lines at various concentrations and showed good hepatocyte-targeting ability. Furthermore, GPCS/DNA complexes showed higher levels of GFP expression in the liver in model mice after intravenous injection than naked DNA and metoxy-poly(ethylene glycol)-chitosan-graft-spermine as controls without remarkable fibrosis, inflammation, lipidosis, or necrosis. In a tumor suppression study, an intravenous injection of the GPCS/. Pdcd4 complexes significantly suppressed tumor growth, activated apoptosis, and suppressed proliferation and angiogenesis in liver tumor-bearing H-ras12V mice. Our results indicate that the GPCS copolymer has potential as a hepatocyte-targeting gene carrier.
Keyword
Galactosylated poly(ethylene glycol)-chitosan-graft-spermineGene therapyHepatocyte targetingNon-viral gene delivery
ISSN
0142-9612
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.biomaterials.2011.11.024
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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